细胞周期调控蛋白在许多人类恶性肿瘤的发展和进展中起着重要作用。识别它们的生物学功能以及它们的预后效用是一个积极研究的领域。作为阐明透明细胞肾细胞癌（ccRCC）的分子特性的持续努力的延续，我们提出了一项针对cyclin-dependent kinase inhibitor 3（CDKN3）在ccRCC中的预后和机制作用的全面生物信息学研究。通过UCSC Xena浏览器，我们获得了癌症基因组图谱计划的ccRCC队列，以获取CDKN3 mRNA表达数据及其相应的临床病理学变量。使用单变量和多变量Cox回归分析评估CDKN3的独立预后标识。利用基因集富集分析和共表达基因功能注释来识别与CDKN3相关的改变分子通路。使用TIMER 2.0和基因表达谱交互分析评估肿瘤免疫微环境。在癌症基因组图谱计划的ccRCC队列中，CDKN3上调与缩短总生存期（风险比[HR] = 2.325，95％置信区间[CI]：1.703- 3.173，P < .0001）相关。单变量（HR: 0.426，95％CI: 0.316-0.576，P < .001）和多变量（HR: 0.560，95％CI: 0.409-0.766，P < .001）Cox回归分析表明CDKN3是总生存期的独立预后变量。高CDKN3表达与以下通路富集相关，包括移植排斥、上皮间质转化、有丝分裂纺锤体、炎症反应、IL-6/JAK/STAT3信号通路、精子生成、TNF-α/NF-kB通路、补体活化、KRAS信号通路和INF-γ信号。CDKN3还与各种免疫细胞的显著浸润以及与免疫相关基因的显著相关性相关。CDKN3是ccRCC的不良预后生物标志物，会改变多种分子通路并影响肿瘤免疫微环境。版权所有 © 2023作者。 Wolters Kluwer Health, Inc.出版。

Cell cycle regulatory proteins plays a pivotal role in the development and progression of many human malignancies. Identification of their biological functions as well as their prognostic utility presents an active field of research. As a continuation of the ongoing efforts to elucidate the molecular characteristics of clear cell renal cell carcinoma (ccRCC); we present a comprehensive bioinformatics study targeting the prognostic and mechanistic role of cyclin-dependent kinase inhibitor 3 (CDKN3) in ccRCC. The ccRCC cohort from the Cancer Genome Atlas Program was accessed through the UCSC Xena browser to obtain CDKN3 mRNA expression data and their corresponding clinicopathological variables. The independent prognostic signature of CDKN3 was evaluated using univariate and multivariate Cox logistic regression analysis. Gene set enrichment analysis and co-expression gene functional annotations were used to discern CDKN3-related altered molecular pathways. The tumor immune microenvironment was evaluated using TIMER 2.0 and gene expression profiling interactive analysis. CDKN3 upregulation is associated with shortened overall survival (hazard ratio [HR] = 2.325, 95% confident interval [CI]: 1.703-3.173, P < .0001) in the Cancer Genome Atlas Program ccRCC cohort. Univariate (HR: 0.426, 95% CI: 0.316-0.576, P < .001) and multivariate (HR: 0.560, 95% CI: 0.409-0.766, P < .001) Cox logistic regression analyses indicate that CDKN3 is an independent prognostic variable of the overall survival. High CDKN3 expression is associated with enrichment within the following pathways including allograph rejection, epithelial-mesenchymal transition, mitotic spindle, inflammatory response, IL-6/JAK/STAT3 signaling, spermatogenesis, TNF-α signaling via NF-kB pathway, complement activation, KRAS signaling, and INF-γ signaling. CDKN3 is also associated with significant infiltration of a wide spectrum of immune cells and correlates remarkably with immune-related genes. CDKN3 is a poor prognostic biomarker in ccRCC that alters many molecular pathways and impacts the tumor immune microenvironment.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.